Recurrent cholangitis and bacteraemia due to Edwardsiella tarda: a case report

Abstract Edwardsiella tarda is typically isolated from aquatic environments. It rarely causes infections in humans. Edwardsiella tarda infections in humans result from the consumption of infected or contaminated food. Here, we present a case of recurrent cholangitis and bacteraemia associated with E. tarda. An 82-year-old man with no history of seafood inoculation was admitted to our hospital because of difficulty in moving his body. The patient was diagnosed with cholangitis, and the blood culture revealed the presence of E. tarda. The patient underwent bile duct stenting and received antibiotic therapy for 14 days. Forty-four days after discharge, cholangitis recurred, and blood culture again showed the presence of E. tarda. The patient underwent bile duct stenting and antibiotic therapy for 11 days. No cholangitis or bacteraemia associated with E. tarda was observed in the following 3 years. Our case strongly suggests that colonization with E. tarda results in recurrent cholangitis and bacteraemia.


INTRODUCTION
Edwardsiella tarda, a gram-negative facultative anaerobe that is a member of the family Enterobacteriaceae, is typically isolated from aquatic environments and water-dwelling animals [1,2].Edwardsiella tarda rarely causes infections in humans [1,2].However, the prognosis of bacteraemia caused by E. tarda is extremely poor, with a mortality rate of 44.6% [1].It is unclear whether this bacterium persists in the human body.Moreover, reinfection with E. tarda has not been reported.Here, we present a case of shortterm recurrent cholangitis and bacteraemia associated with E. tarda.

CASE REPORT
An 82-year-old male was brought to the emergency department because of difficulty in moving his body.He had a history of cholangitis, and a bile duct stent was placed a year prior; however, the stent was not replaced because the patient refused to attend the hospital.He has not received any antibiotic treatment for a year since then.He has a history of atrial fibrillation (on rivaroxan medication), chronic heart failure, hypertension, chronic kidney disease, and hyperuricaemia.The patient had no history of seafood inoculation or contact with aquatic environments.
On arrival at the emergency department, his temperature was 38.7 • C; blood pressure, 116/86 mmHg; pulse rate, 75 beats/min; and oxygen saturation, 97% on room air.The patient was alert and had icteric sclerae but no rash or lymphadenopathy.His abdomen was soft; however, tenderness was noted over the right hypochondrium.Laboratory data revealed an increased inf lammatory response and elevated hepatobiliary enzyme levels (Table 1).Computed tomography revealed dilated intrahepatic bile ducts (Fig. 1a and b).
We diagnosed cholangitis associated with stent obstruction and performed endoscopic retrograde cholangiopancreatography to replace the bile duct stent (Flexima™ Biliary Stent System 7Fr 10 cm; Boston Scientific, Marlborough, Massachusetts, United States) (Fig. 2).Empiric antibiotic therapy with meropenem (1 g IV q12h) was initiated after two sets of blood cultures were obtained and Edwardsiella tarda and Aeromonas caviae were detected.The patient was admitted to the high care unit because of progressive decrease in blood pressure and the need for vasopressors.Afterwards, the infection was under control, so on day 8 the antibiotic was changed to Augmentin (amoxicillin/clavulanate; 500/125 mg PO q8h) which has good bioavailability and continued for 7 days (the total duration of antibiotic treatment was 14 days).The patient was discharged on day 12.  Forty-four days after discharge, the patient was admitted to the emergency department, with symptoms similar to those observed previously.On arrival at the emergency department, his temperature was 39.4 • C; blood pressure, 83/54 mmHg; pulse rate, 71 beats/min; and oxygen saturation, 90% on room air.The patient had a Glasgow Coma Scale score of E4V3M5, with impaired consciousness and icteric sclerae but no rash or lymphadenopathy.The abdomen was soft; however, the right hypochondrium was tender.Laboratory data revealed an increased inf lammatory response and elevated hepatobiliary enzyme levels (Table 1).Computed tomography revealed dilated intrahepatic bile ducts.We diagnosed cholangitis associated with stent obstruction and performed endoscopic retrograde cholangiopancreatography; the biliary stent was replaced again (Flexima™ Biliary Stent System 7Fr 10 cm; Boston Scientific).Empiric antibiotic therapy with tazobactam/piperacillin (4.5 g IV q8h) was initiated after two sets of blood cultures were obtained, and E. tarda was detected.The sensitivity results showed that ampicillin and cefaclor changed from sensitive (in the previous culture results) to intermediate and resistant (Table 2).The amylase level increased from 135 U/l on admission to 1036 U/l on day 3, suggesting possible gallstone pancreatitis.Endoscopic sphincterotomy was performed, and bile duct stones were excised.On day 5, a suspected drug rash caused by tazobactam/piperacillin occurred, and the antibiotic was changed to levof loxacin (500 mg × 1 IV, followed by 250 mg q24h), which was continued for 7 days (the total duration of antibiotic treatment was 11 days).The patient was discharged on day 11.
Since then, the patient has not experienced a recurrence of cholangitis or bacteraemia due to E. tarda for 3 years.

DISCUSSION
Edwardsiella tarda is a relatively rare human pathogen commonly found in freshwater or brackish water environments, such as estuaries [1,2].Edwardsiella tarda is detected in 0.02% of blood cultures [3] and rarely causes infections in humans.Edwardsiella tarda infections in humans result from the consumption of infected or contaminated food, such as fish [1].The gastrointestinal tract is the most commonly affected organ by E. tarda [2,4].Extraintestinal infections, such as cholangitis, have been reported less frequently [1].
As discussed below, this patient was considered to be at high risk of cholangitis and bacteraemia associated with E. tarda.Age ≥65 years is significantly associated with an increased risk of E. tarda bacteraemia [3], and the main underlying conditions in E. tarda bacteraemia are hepatobiliary disease (liver cirrhosis, gallbladder stones, and ethanol abuse), malignancy, and iron overload status (sickle cell disease, leukaemia, and neonatal condition) [1,4].
In this case, the patient had recurrent cholangitis and bacteraemia associated with E. tarda within a short period, strongly suggesting colonization with E. tarda.To the best of our knowledge, this is the first reported case of recurrent E. tarda bacteraemia and cholangitis.Little is known about the current prevalence of E. tarda colonization.A study conducted in the 1970s [5] reported that only 26 out of 353 600 (0.007%)Japanese individuals were healthy carriers of E. tarda in their digestive tract.Based on the duration of antibiotic treatment for severe cholangitis, treatment for 4-7 days with clinical resolution has been suggested [6].The median duration of antibiotic treatment for E. tarda-associated bacteraemia is reported to be 12 days [3], and the duration of our treatment for E. tarda-associated bacteraemia was considered sufficient (14 days).

CONCLUSION
Here, we report a case of recurrent cholangitis and bacteraemia caused by E. tarda.The colonization rate of E. tarda in the human body is low; however, our results strongly suggest that E. tarda colonization causes recurrent cholangitis and bacteraemia.

Table 2 .
Antibiotic susceptibility of Edwardsiella tarda from blood culture MIC, minimum inhibitory concentration.